Willett Nick J, Thote Tanushree, Lin Angela S P, Moran Shamus, Raji Yazdan, Sridaran Sanjay, Stevens Hazel Y, Guldberg Robert E
Arthritis Res Ther. 2014 Feb 6;16(1):R47. doi: 10.1186/ar4476.
Micronized dehydrated human amnion/chorion membrane (μ-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of μ-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of μ-dHACM would attenuate OA progression.
Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. Twenty four hours post-surgery, μ-dHACM or saline was injected intra-articularly into the rat joint. Naïve rats also received μ-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-μCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery.
There was no measured baseline effect of μ-dHACM on cartilage in naïve animals. Histological staining of treated joints showed presence of μ-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with μ-dHACM. EPIC-μCT analysis quantitatively showed that μ-dHACM reduced proteoglycan loss in MMT animals.
μ-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of μ-dHACM may have a therapeutic effect on OA development.
微粉化脱水人羊膜/绒毛膜(μ-dHACM)源自捐赠的人胎盘,具有抗炎、低免疫原性和抗纤维化特性。本研究的目的是定量评估μ-dHACM作为骨关节炎(OA)大鼠模型中疾病修饰干预措施的疗效。假设关节内注射μ-dHACM会减缓OA进展。
对Lewis大鼠进行内侧半月板横断(MMT)手术以诱导OA。术后24小时,将μ-dHACM或生理盐水关节内注射到大鼠关节中。未处理的大鼠也接受μ-dHACM注射。术后21天使用离子造影剂平衡分配法(EPIC-μCT)评估胫骨关节软骨的微观结构变化。术后3天和21天还对关节进行组织学评估,并分析滑膜液中的炎症标志物。
在未处理的动物中,未测量到μ-dHACM对软骨的基线效应。处理后关节的组织学染色显示,术后3天和21天滑膜中有μ-dHACM存在,同时伴有局部细胞增多。在MMT动物中,μ-dHACM治疗可预防21天时软骨损伤的发生,并显著减少部分侵蚀的数量。EPIC-μCT分析定量显示,μ-dHACM减少了MMT动物中蛋白聚糖的损失。
关节内注射后,μ-dHACM迅速被滑膜摄取,并减缓大鼠OA模型中的软骨降解。这些数据表明,关节内递送μ-dHACM可能对OA发展具有治疗作用。